Psilocybin for Opioid Use Disorder

Overseen By Anna Rose Childress, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Anna Rose Childress, Ph.D.

Must be taking: Buprenorphine, Methadone

Must not be taking: Antidepressants, others

Disqualifiers: Schizophrenia, Bipolar, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

24 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to test addiction-related brain circuitry (motivation/reward and inhibition) as well as neurocognitive circuitry prior to and following low or high dose psilocybin (PEX010 from Filament). Using fMRI, we will examine brain circuits relevant to drug relapse as well as neurocognitive flexibility circuits in individuals with opioid use disorder. We will randomize 24 males and females, aged 18 - 60, in the greater Philadelphia area, to either 1mg or 25 mg of psilocybin. Participants will 1. come to our offices for screening visits - these are assessments, interviews, and some medical tests (such as a history and physical, as well as a fasting blood draw) to help us determine eligibility for our study. 2. If not already in an inpatient setting, participants be admitted to an inpatient program for the duration of the psilocybin phases - about two weeks. During this time, they will be brought to our offices at 3535 Market Street in Philadelphia for about 7 visits. These visits include pre-dose psilocybin preparation therapy, baseline assessments and neuropsychological testing, psilocybin dosing, post dose therapy visits, and post dose assessments.

Will I have to stop taking my current medications?

The trial requires participants to stay on their current opioid treatment medications like BUP-NX or methadone. However, you cannot take any psychoactive medications, such as antidepressants, during the study.

What data supports the effectiveness of the drug psilocybin for treating opioid use disorder?

Research suggests that psilocybin, a component of 'magic mushrooms', may help treat addiction disorders, including smoking and potentially methamphetamine use, by providing therapeutic benefits without the risk of addiction or overdose. Additionally, psilocybin has shown promise in treating major depressive disorder, indicating its potential effectiveness in addressing various mental health and substance use issues. ^{1 2 3 4 5}

Is psilocybin generally safe for humans?

Psilocybin is generally considered safe when used in a controlled setting with proper support, although some people may experience challenging psychological effects. In studies, the risk of long-term psychological distress or risky behavior is very low when participants are carefully screened and supported. ^{5 6 7 8 9}

How is the drug psilocybin different from other treatments for opioid use disorder?

Psilocybin is unique because it is a psychedelic substance that may help reduce opioid use disorder by altering perception and consciousness, unlike traditional treatments that often focus on managing withdrawal symptoms or blocking opioid effects. It has shown promise in lowering the odds of opioid use disorder, which is not commonly seen with other treatments. ^{1 10 11 12 13}

Eligibility Criteria

This trial is for men and women aged 18-60 in the Philadelphia area with opioid use disorder. Participants must be able to come to the office for multiple visits, including therapy sessions and medical tests. They'll also need to stay in an inpatient program for about two weeks during the study.

Inclusion Criteria

An informed consent document voluntarily signed and dated by the subject

IQ score of greater than or equal to 80

I am 18-60 years old, healthy, and seeking treatment for opioid addiction.

Exclusion Criteria

Seizure disorder or history of seizures not related to drug or alcohol withdrawal

At Screening or Baseline have elevated blood pressure as defined as: Screening blood pressure SBP greater than 135 mmHg or DBP greater than 85 mmHg on three separate readings; or Baseline blood pressure SBP greater than 140 mmHg or DBP greater than 90 mmHg on three separate readings

I have been diagnosed with bipolar disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits (in-person)

Inpatient Psilocybin Treatment

Participants are admitted to an inpatient program for psilocybin treatment, including pre-dose preparation, dosing, and post-dose therapy

2 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including fMRI and behavioral assessments

8 weeks

Treatment Details

Interventions

• Psilocybin

Trial Overview The study is testing how low (1mg) or high (25mg) doses of psilocybin affect brain circuits related to addiction and cognitive flexibility using fMRI scans before and after dosing. The participants will be randomly assigned to one of these dose groups.

Participant Groups

Group I: High dose psilocybin Experimental Treatment 1 Intervention

25 mg PEX010 capsule, single dose

Group II: Low dose psilobyin Active Control 1 Intervention

1 mg PEX010 capsule, single dose

Who Is Running the Clinical Trial?

Anna Rose Childress, Ph.D.

Lead Sponsor

Trials

3

Recruited

70+

Findings from Research

In a pilot study involving 15 participants, those who underwent psilocybin-facilitated smoking cessation reported significant insights into their self-identity and reasons for smoking, which contributed to their ability to quit smoking.

Participants experienced lasting positive changes beyond smoking cessation, such as increased altruism and pro-social behavior, suggesting that the therapeutic effects of psilocybin may extend beyond the immediate treatment context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts. Noorani, T., Garcia-Romeu, A., Swift, TC., et al.[2019]

Methamphetamine use disorder is a serious condition with high relapse rates and limited effectiveness of current treatments, highlighting the need for new therapeutic options.

Psilocybin-assisted psychotherapy shows promise as a potential treatment for methamphetamine use disorder, based on early experiences from four clinical trials, although no published studies currently exist on this specific application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring psilocybin-assisted psychotherapy in the treatment of methamphetamine use disorder. Brett, J., Knock, E., Korthuis, PT., et al.[2023]

Psilocybin, found in 'magic mushrooms', shows promise as a non-addictive alternative for treating mental health disorders like major depressive disorder and addiction, potentially addressing the urgent need for new therapies amid rising addiction and suicide rates.

Current research indicates that psilocybin may offer therapeutic benefits without the overdose risks associated with traditional mind-altering substances, suggesting a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin Therapeutic Research: The Present and Future Paradigm. Kargbo, RB.[2021]

In a study of 27 patients with moderate to severe major depressive disorder, psilocybin-assisted treatment showed significant and lasting antidepressant effects, with 75% of participants experiencing a treatment response and 58% achieving remission after 12 months.

There were no serious adverse events related to psilocybin, indicating a favorable safety profile, and participants reported meaningful personal and spiritual experiences that correlated with increased well-being, although these did not directly predict improvements in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Gukasyan, N., Davis, AK., Barrett, FS., et al.[2022]

A systematic review of 16 studies found that psilocybin is generally well-tolerated, with the most common side effects being transient nausea and headache, and no reports of severe long-term issues like psychosis.

Psilocybin shows promise as a safe treatment option for psychiatric and substance-dependence conditions, particularly for patients who do not respond to standard therapies, as it has demonstrated both acute and long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Tolerability and Safety of Psilocybin in Psychiatric and Substance-Dependence Conditions: A Systematic Review. Kaminski, D., Reinert, JP.[2023]

In a survey of 1993 individuals who experienced challenging psilocybin trips, 39% rated their experience as one of the most difficult of their lives, with 11% reporting risks of physical harm, particularly influenced by dose and lack of support.

Despite the challenges, 84% of respondents felt they benefited from the experience, suggesting that while adverse effects can occur, the overall incidence of serious psychological distress is low, especially in controlled settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Carbonaro, TM., Bradstreet, MP., Barrett, FS., et al.[2018]

Psilocybin has shown significant therapeutic effects in reducing symptoms of depression and anxiety in patients with life-threatening diseases, based on a systematic review and meta-analysis of clinical trials involving 92 patients.

The results indicate that psilocybin may be a safe and effective treatment option, particularly for cases resistant to conventional therapies, with significant improvements measured by the Beck Depression Inventory and State-Trait Anxiety Inventory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. Vargas, AS., Luís, Â., Barroso, M., et al.[2020]

Lifetime use of psilocybin is associated with significantly lower odds of developing opioid use disorder (OUD), with an adjusted odds ratio of 0.70 based on a large sample of 214,505 participants from the National Survey on Drug Use and Health.

Psilocybin use was linked to reduced odds of meeting seven out of eleven DSM-IV criteria for OUD, suggesting its potential as a therapeutic option, although further clinical trials are necessary to establish a causal relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations between classic psychedelics and opioid use disorder in a nationally-representative U.S. adult sample. Jones, G., Ricard, JA., Lipson, J., et al.[2022]

In a proof-of-concept study involving 10 alcohol-dependent participants, psilocybin administration led to a significant increase in abstinence rates after treatment, with effects maintained for up to 36 weeks.

Participants experienced no significant adverse events, suggesting that psilocybin is safe for use in this context, and the intensity of the psilocybin effects predicted positive changes in drinking behavior and cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. Bogenschutz, MP., Forcehimes, AA., Pommy, JA., et al.[2022]

A study involving 28 Black individuals with Opioid Use Disorder revealed that while most had heard of psilocybin, only a small number had actually used it, indicating limited exposure to this potential treatment.

Despite a willingness to consider psilocybin therapy, over 80% of participants perceived significant risks associated with its use, highlighting the need for culturally informed education and outreach to improve understanding and acceptance of psilocybin as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin use patterns and perception of risk among a cohort of Black individuals with Opioid Use Disorder. Clifton, JM., Belcher, AM., Greenblatt, AD., et al.[2023]

Psilocybin, a serotonergic psychedelic, has shown promise in treating various psychiatric disorders, including depression and substance use disorders, with 9 clinical trials conducted between 2000 and 2020.

The treatment is generally well tolerated with limited side effects, and some patients with treatment-resistant conditions have experienced significant long-term improvements after just a few sessions, indicating its potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. Breeksema, JJ., Koolen, MHB., Somers, M., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Exploring psilocybin-assisted psychotherapy in the treatment of methamphetamine use disorder. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Psilocybin Therapeutic Research: The Present and Future Paradigm. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The Tolerability and Safety of Psilocybin in Psychiatric and Substance-Dependence Conditions: A Systematic Review. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Optimal dosing for psilocybin pharmacotherapy: Considering weight-adjusted and fixed dosing approaches. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Hallucinogenic mushrooms. [2017]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Associations between classic psychedelics and opioid use disorder in a nationally-representative U.S. adult sample. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. [2022]

12. Hungary pubmed.ncbi.nlm.nih.gov

Psilocybin use patterns and perception of risk among a cohort of Black individuals with Opioid Use Disorder. [2023]

13. Netherlands pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. [2021]